Document Detail


Posttranslational regulation of NO synthase activity in the renal medulla of diabetic rats.
MedLine Citation:
PMID:  15383397     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Shear stress increases nitric oxide (NO) production by endothelial cells, inner medullary collecting duct cells, and thick ascending limb. We postulated that the osmotic diuresis accompanying type 1 diabetes is associated with increased NO synthase (NOS) activity and/or expression in the renal medulla. Diabetes was induced by injection of streptozotocin, with insulin provided to maintain moderate hyperglycemia (Hyp) or euglycemia (Eug) for 3 wk. Sham rats received vehicle treatments. A separate group of rats (Phz) received phlorizin to produce a glucose-dependent osmotic diuresis. Renal medullary NOS1 and NOS2 activities did not differ between groups, whereas NOS3 activity was significantly increased in Hyp. Neither NOS1 nor NOS3 protein levels differed significantly between groups. Reduced phosphorylation of NOS3 at Thr(495) and Ser(633) was evident in medullary homogenates from Hyp rats, with no difference apparent at Ser(1177). Immunohistochemical analysis indicated prominent expression of pThr(495)NOS3 in the thick ascending limb and collecting duct of Sham and Phz rats. Hyp rats displayed staining in the collecting duct but minimal thick ascending limb staining. Immunostaining with anti-pSer(1177)NOS3 was evident only in the thick ascending limb, with no apparent differences between groups. In summary, glucose-dependent osmotic diuresis alone did not alter NOS activity or expression in the renal medulla. Diabetic hyperglycemia increased medullary NOS3 activity without a concomitant increase in NOS3 protein levels; however, NOS3 phosphorylation was reduced at Thr(495) and Ser(633). Thus changes in the phosphorylation of NOS at known regulatory sites might represent the primary mechanism underlying increased renal medullary NOS activity in diabetic hyperglycemia.
Authors:
Dexter L Lee; Jennifer M Sasser; Janet L Hobbs; Amy Boriskie; David M Pollock; Pamela K Carmines; Jennifer S Pollock
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2004-09-21
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  288     ISSN:  1931-857X     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-12-07     Completed Date:  2005-03-04     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F82-90     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Diabetes Mellitus, Experimental / enzymology*
Kidney Medulla / enzymology*
Male
Nitric Oxide Synthase / metabolism*
Phlorhizin
Phosphorylation
Polyuria / chemically induced,  enzymology
Protein Processing, Post-Translational / physiology*
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
DK-63416/DK/NIDDK NIH HHS; HL-60653-S1/HL/NHLBI NIH HHS; R21 DK063416/DK/NIDDK NIH HHS; R21 DK063416-01/DK/NIDDK NIH HHS; R21 DK063416-02/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
CU9S17279X/Phlorhizin; EC 1.14.13.39/Nitric Oxide Synthase
Comments/Corrections

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